imprinting disorders

Question 1

why are gynogenetic or androgenetic diploids inviable?

Answer 1

due to genomic imprinting

Question 2

what side is IGF-11 controlled by?

Answer 2

paternal side- is maternally imprinted

Question 3

what side is IGFIIR controlled by?

Answer 3

maternal side

Question 4

what phenotype to mice with a IGF11 mutation transmitted down the paternal line have?

Answer 4

growth defects

Question 5

what is maternal imprinting?

Answer 5

allele inherited from the mother is transcriptionally silent, phenotype is governed by paternal side

Question 6

what two situations can lead to imprinting diseases?

Answer 6

both copies of the gene are silenced or mutations in the expressed alllele

Question 7

what causes Beckwith-Weirdemann syndrome?

Answer 7

maternal igf2 allele on chromosome 11 is not silenced due to imprinting defect in IC1. hypomethylation at potassium channel DMR region

Question 8

what are the symptoms of BWS?

Answer 8

pediatric overgrowth, predisposition to tumours

Question 9

inheritance pattern of BWS?

Answer 9

paternally inherited

Question 10

symptoms of anglemans?

Answer 10

development difficencies, sleep disorders, seizures

Question 11

inheritance pattern of anglemans?

Answer 11

maternally inherited, paternally imprinted chromosome 15

Question 12

genetic causes of anglemans

Answer 12

deletions of PW region, point mutations in maternal UBE3a or paternal UPD

Question 13

symptoms of prader willi

Answer 13

obesity, behaviour and cognitive problems

Question 14

inheritance pattern of PW

Answer 14

paternally inheirted, maternally imprinted chromosome 15

Question 15

genetic causes of PW

Answer 15

70% PW region deletion, 25% maternal UPD, mutations in ICR or translocations that separate ICR from PW region

Question 16

symptoms of silver russel

Answer 16

pre and postnatal growth retardation, small triangular face, sweaty head and cardiac defects

Question 17

genetic causes of silver russel

Answer 17

maternal UPD of chromosome 7, maternal duplication of 11p15, hypomethylation of telomeric 11p15 IC- supresses IGF2 expression

Question 18

what is H3K14ac a docking site for

Answer 18

bromo-domain proteins

Question 19

what genes are associated with birth size?

Answer 19

paternally expressed IGF2 and maternally expressed H19

Question 20

why does epigenetic reprogramming take place in PGCs

Answer 20

resets imprinted genes for sex-specific reacquision, erases parental acquired epigenetic memories, facilitates gametogenesis, maintains silenicing of transposbale elements, reduces germline mutation rate

Question 21

why does reprogramming take place in pre-implantation embryo

Answer 21

resets zygotic marks for naive pluripotency, maternal v paternal genome wars- allows more contribution from females

Question 22

how are PGC epigenentic memories erased?

Answer 22

global DNA demethylation, genomic imprint erasure, x chromsoomes reactivation and reorganisation of histones

Question 23

after pGC development what happens to XY and XX germ cells?

Answer 23

XY enter mitotic arrest, XX enter meiosis

Question 24

when does remethylation occur in males and females?

Answer 24

in SSCs in males and after birth in growing oocytes in females

Question 25

what happens to ICRs in PGC resetting?

Answer 25

imprints erased and resestabilished in sex specific manner later in development

Question 26

how are embyros reset in females?

Answer 26

through replication dependent passive mechanisms- PRDMI and PRDM14 repress DMNT3a and b and UHRF1. UHRF1 normally activates DNMT1

Question 27

how are embryos reset in males? a

Answer 27

active mechanisms- 5mC converted to 5hmC by TETs then removed in passive way or by base excision repair

Question 28

how may imprints escape erasure during embryo restting?

Answer 28

these regions have higher numberrr KAP1 binding regions and may recruit DNMT1

Question 29

why did dolly die young?

Answer 29

no restting of epigenetic marks, would not be pluripotent, demethylated in a non-speicifc and delayed way.

Question 30

steps in artificial gamete production

Answer 30

1perform SCNT on somatic cell and induce embyro development in vitro 2. extract ESC from blastocyst 3 induce gametogenesis in vitro 4 use gamete to fertilise partners egg/sperm 5 develop embryo and implant into mother

Question 31

what are man made mouse eggs made from?

Answer 31

in vitro system of generating a mouse oocyte from fibroblast derived pluripotent stem cells

Question 32

how are bimaternal mice made?

Answer 32

oocyte activated, isolate parthenogenetic haploid ESCs, demethylate cells in media- loss of methylation non-specifc, then delete paternally imprinted regions- found that deleting 3 regions made basically normal mice, then implant haploid ESC into mature oocyte

Question 33

how are bipaternal mice made?

Answer 33

mature oocyte enucleated and fertilised with sperm, androgenetic haploid ESCs isolated, demethylate in media, deleting 6 maternally imprinted regions still resullted in death, then coinject haploid ESC and sperm into enucleated oocyte.